Lyme disease is a bacterial infection caused by pathogenic spirochetes of the genus Borrelia. The infection can occur in humans, dogs, deer, mice and other animals, and is transmitted by arthropod vectors, most notably ticks of the genus Ixodes. Borrelia burgdorferi, the most common cause of Lyme disease in North America, was first cultured in 1982. Borrelia are introduced into the host at the site of the tick bite and this is also the location of the initial characteristic skin lesion, erythema chronicum migrans (ECM). In dogs, Lyme disease manifests with arthritis-induced lameness, anorexia, fever, lethargy, lymphadenopathy, and in some cases, fatal glomerulonephritis. A recent study revealed that the percentage of actively infected dogs in endemic areas can be as high as 11%.
The infection may be treated at any time with antibiotics such as penicillin, erythromycin, tetracycline, and ceftriaxone. Once infection has occurred, however, the drugs may not purge the host of the spirochete, but may only act to control the chronic forms of the disease. Complications such as arthritis and fatigue may continue for several years after diagnosis and treatment.
The canine Lyme disease vaccines were developed to provide protection by primarily inducing OspA borreliacidal antibodies. B. burgdorferi OspC is another potential target for borreliacidal antibody-mediated immunity. This protein appears to have an epitope that is responsible for inducing borreliacidal antibodies, and is not conserved among the pathogenic Borrelia spp. Although the specific function of the OspC protein remains unknown, it has been suggested that OspC expression is required for infection of mammals, but not for infection of ticks. Borrelia express OspC shortly after the tick begins feeding, and must continue to express OspC in order to establish an infection in mammals. Therefore, the “window of effectiveness” of the OspC borreliacidal antibodies is increased significantly, compared to OspA borreliacidal antibodies.
Callister et al., (U.S. Pat. Nos. 6,210,676 and 6,464,985, incorporated by reference herein) have suggested employing an immunogenic polypeptide fragment of OspC, alone or in combination with an OspA polypeptide, to prepare a vaccine to protect humans and other mammals against Lyme disease. Livey et al. (U.S. Pat. No. 6,872,550, incorporated by reference herein) also proposed a vaccine for immunizing against Lyme disease prepared from a combination of recombinant OspA, OspB, and OspC proteins.
However, at least two obstacles need to be overcome before a successful vaccine can be created. First, there are over twenty OspC phylotypes, and it is unclear which ones should be included into a vaccine. Second, suitable epitopes for development of borreliacidal anti-OspC antibodies need to be determined.
Therefore, there remains a longstanding need in the art for an improved vaccine to protect mammals, and especially canines, from Lyme disease.